Background:  Tenofovir DF (TDF) is not approved for use in HIV-infected patients <18 years of age. However, widespread use in HIV-infected children and our previous findings of decreased bone mineral density in a substantial minority of children treated with TDF, led us to design this open-label trial evaluating lumbar spine bone mineral density during and following treatment with TDF-containing HAART in HIV-infected children.

Methods:  Baseline dual-energy X-ray absorptiometry (DEXA) scans were performed on 6 treatment-experienced HIV-infected children (median age 12.8 year, range 11.3 to 17.5) had prior to receiving 300 mg TDF (median 268 mg/m², range 208 to 345) as part of HAART that included a ritonavir-boosted protease inhibitor. Physical examinations, Tanner staging, routine laboratory studies, and DEXA scans were performed at 12, 24, and 48 weeks and later time-points in some. Children requiring discontinuation of TDF due to decreased bone mineral density had follow-up measurements performed to assess recovery.

Results: Of 6 children, 5 experienced absolute decreases in bone mineral density, despite linear growth, that were sustained to week 48. With 2 exceptions, the range of decreases was small (1 to 5%), but resulted in worsening bone mineral density status compared to age, ethnicity, and gender-matched controls. The 2 subjects who experienced much greater bone mineral density decreases were pre-pubertal. Subject #1 was the smallest child and thus received the highest dose/m² of TDF. She experienced an absolute bone mineral density decrease compared to baseline of 20% at 12 weeks and 27% at 24 weeks, necessitating withdrawal of TDF but continuation of the rest of her HAART. By the following year her bone mineral density had recovered to 2% below baseline. Subject #2 experienced a 10% decline in bone mineral density by week 24. Recovery almost back to baseline was associated with a 1.3 log increase in viral load, presumably secondary to non-adherence. Absolute bone mineral density measured 60 weeks after starting therapy was 6% below baseline.

Conclusions:  Based upon this small study and our previous findings, TDF-containing HAART is associated with bone mineral density loss, which tends to occur in pre-pubertal children or those in early puberty and seems to partially recover with discontinuation of TDF. Higher TDF exposure in smaller children, who must take the adult formulation of the drug, because a pediatric formulation is not available, may also contribute to the degree of bone mineral density loss. Careful monitoring of HIV-infected children requiring treatment with TDF is warranted.